The intention is to continue our in vivo studies of ontogeny, specificity, recirculation, localization and effector function for the virus-immune cytotoxic T cell. Thymocytes from neonatal (3-day-old) mice and radiation chimeras (28 day) can be stimulated stongly with vaccinia virus on adoptive transfer into irradiated recipients. These protocols are being used extensively to study the influence of different major histocompatibility complex (MHC) combinations, tolerance states, irradiation protocols and drug treatments on the development of responder potential. Attention is also being given to the mechanism underlying the loss of thymic competence which occurs generally in aging mice and in P1 greater than (P1xP2)F1 chimeras. The specificity of effector T cells is being examined using radiation chimeras and negative selection protocols, in association with clonal assay procedures (continuous cells lines and limit dilution). Studies will be made of the entry into, and exit from, the recirculating pool for thymocytes and other lymphoid cells. Effector populations will be characterized suing models which allow examinqation of inflammatory exudates in cerebrospinal fluid of mice that have grown either viruses or tumor cells in the central nervous system. The aim is thus to make a clear and careful analysis of the life history of the virus-immune, effector T cell. this will be related to questions that are generated from consideration of practical problems in theraphy and disease process, and to arguments and reagents developed from other areas of basic immunology. Particular attention will be given to the analysis of thost response in mice infected with extromelia (mouse pox) and Sendai virus. This proposal is unique from two aspects: 1) We are the only group in the world currently analyzing the recirculation of virus immune T cells in the mouse using thoracic duct cannulation techniques. 2) The John Curtin School of Medical Research is the only first-rate, academic institution that has consistently studied host-response to ectromelia (mouse pox) virus.